Study Reveals New Method to Delay Evolution of Drug Resistance in Malaria Parasite

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A new method that effectively delays the evolution of drug resistance in malaria parasites has been devised by researchers at the University of Florida.

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David Smith, associate director of disease ecology at UF's Emerging Pathogens Institute and study's co-author, said that the new research would help scientists and policy makers in extending the longevity of current artemisinin-based malaria drugs combined with partner drugs.

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Smith and colleagues created mathematical models assessing the strategic effectiveness and clinical outcomes of using one, two and three first-line drug therapies to treat malaria within a population over a 20-year period.

They found that using two or three drugs simultaneously reduced the total clinical cases and number of failed treatments, and slowed the rate at which drug-resistant genes spread within the parasites that cause malaria: Plasmodium falciparum, P. vivax, P. malariae and P. ovale.

"The models indicate that we can slow the evolution of resistance to current artemisinin-based therapies if nations use them in combination with two or more partner drugs," Smith said.

Smith said that artemisinin-combined therapies, or ACTs, are currently not widely implemented due to operational challenges and expense. However, he said that the study offers compelling evidence for global leaders to collaborate and overcome these issues.

"This is not to say that implementing multiple first-line therapies solves all of our malaria problems. Anti-malarial drug development needs to continue so that we have novel and highly effective anti-malarials that can be plugged into the recommended strategy of deploying multiple therapies," Boni said.

Artemesinin drugs, derived from the herb Artemisia annua, are relatively new and the malaria parasite does not yet appear to have a resistance to it. They work by triggering chemical reactions, which damage the Plasmodium parasite.

"We don't have anything in the pipeline after ACTs, and it's basically just a matter of time until drug resistance evolves and artemisinin also fails. So the question becomes how do we keep ACTs in our arsenal for as long as effectively possible?" Smith said.

The researchers' models also show that cycling through single drugs accelerated the rate at which malaria parasites evolved drug resistance.

Smith said this occurred because cycling a single drug degraded the parasite's average fitness, which made it easier for drug-resistant genes to spread throughout the parasite population.

The cycling models predicted a declining therapeutic value of a single drug within 3.54 years, versus a longer effective therapeutic value of 9.95 years when three drugs were used in equal proportions within a population.

"Using multiple first-line drugs reduces the selection pressure for resistance to a single drug. This is one way to make the ACTs last longer and benefit more people," Smith said.

The study is scheduled to publish online this week in the Proceedings of the National Academy of Sciences and in print on Sept. 16.

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